Discovery of New DNA Topoisomerase II Inhibitors using Structure Based Virtual Screening Method
DNA topoisomerases are proved therapeutic targets of anticancer and antibacterial drugs. Structures of topoisomerase–DNA and inhibitor ternary complexes have revealed the exact binding sites and mechanisms of topoisomerase poisons. There are two isoforms of Human Topoisomerase II; α and β. Both of t...
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Format: | Article |
Language: | English |
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Turkish Chemical Society
2019-05-01
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Series: | Journal of the Turkish Chemical Society, Section A: Chemistry |
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Online Access: | http://dergipark.gov.tr/jotcsa/issue/42264/466457 |
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author | Tugba Ertan-Bolelli Kayhan Bolelli |
author_facet | Tugba Ertan-Bolelli Kayhan Bolelli |
author_sort | Tugba Ertan-Bolelli |
collection | DOAJ |
description | DNA topoisomerases are proved therapeutic targets of anticancer and antibacterial drugs. Structures of topoisomerase–DNA and inhibitor ternary complexes have revealed the exact binding sites and mechanisms of topoisomerase poisons. There are two isoforms of Human Topoisomerase II; α and β. Both of them perform similar functions and their levels differ depending on the replicative activity and type of tissue. Topo IIα is preferentially expressed in proliferating cells. Thus selective Topo IIα inhibitors have been of particular interest in cancer therapy, as they may represent a more targeted approach to highly proliferative cells.
In this study, we use structure based virtual screening method with molecules which are commercially available in the ZINC database. Docking studies were performed by Glide module available in Schrödinger software, Ligand filtration was also done to obtain an efficient collection of hit molecules by employing Lipinski “rule of five” and pharmacokinetic properties of the compounds were tested using Qikprop module. From approximately ten thousand compounds from Zinc database it was possible to select 4 top chemical structures with good inhibiting profile for topo II, with suitable ADME/Tox properties, thus comp. 1-4 could be the promising inhibitors of human topo IIα enzyme. |
first_indexed | 2024-04-10T12:52:15Z |
format | Article |
id | doaj.art-fa825007bb6c48059a9e79459270f057 |
institution | Directory Open Access Journal |
issn | 2149-0120 |
language | English |
last_indexed | 2024-04-10T12:52:15Z |
publishDate | 2019-05-01 |
publisher | Turkish Chemical Society |
record_format | Article |
series | Journal of the Turkish Chemical Society, Section A: Chemistry |
spelling | doaj.art-fa825007bb6c48059a9e79459270f0572023-02-15T16:13:44ZengTurkish Chemical SocietyJournal of the Turkish Chemical Society, Section A: Chemistry2149-01202019-05-0161717810.18596/jotcsa.466457Discovery of New DNA Topoisomerase II Inhibitors using Structure Based Virtual Screening MethodTugba Ertan-BolelliKayhan BolelliDNA topoisomerases are proved therapeutic targets of anticancer and antibacterial drugs. Structures of topoisomerase–DNA and inhibitor ternary complexes have revealed the exact binding sites and mechanisms of topoisomerase poisons. There are two isoforms of Human Topoisomerase II; α and β. Both of them perform similar functions and their levels differ depending on the replicative activity and type of tissue. Topo IIα is preferentially expressed in proliferating cells. Thus selective Topo IIα inhibitors have been of particular interest in cancer therapy, as they may represent a more targeted approach to highly proliferative cells. In this study, we use structure based virtual screening method with molecules which are commercially available in the ZINC database. Docking studies were performed by Glide module available in Schrödinger software, Ligand filtration was also done to obtain an efficient collection of hit molecules by employing Lipinski “rule of five” and pharmacokinetic properties of the compounds were tested using Qikprop module. From approximately ten thousand compounds from Zinc database it was possible to select 4 top chemical structures with good inhibiting profile for topo II, with suitable ADME/Tox properties, thus comp. 1-4 could be the promising inhibitors of human topo IIα enzyme.http://dergipark.gov.tr/jotcsa/issue/42264/466457anticancer activitydockingtopoisomerasevirtual screening |
spellingShingle | Tugba Ertan-Bolelli Kayhan Bolelli Discovery of New DNA Topoisomerase II Inhibitors using Structure Based Virtual Screening Method Journal of the Turkish Chemical Society, Section A: Chemistry anticancer activity docking topoisomerase virtual screening |
title | Discovery of New DNA Topoisomerase II Inhibitors using Structure Based Virtual Screening Method |
title_full | Discovery of New DNA Topoisomerase II Inhibitors using Structure Based Virtual Screening Method |
title_fullStr | Discovery of New DNA Topoisomerase II Inhibitors using Structure Based Virtual Screening Method |
title_full_unstemmed | Discovery of New DNA Topoisomerase II Inhibitors using Structure Based Virtual Screening Method |
title_short | Discovery of New DNA Topoisomerase II Inhibitors using Structure Based Virtual Screening Method |
title_sort | discovery of new dna topoisomerase ii inhibitors using structure based virtual screening method |
topic | anticancer activity docking topoisomerase virtual screening |
url | http://dergipark.gov.tr/jotcsa/issue/42264/466457 |
work_keys_str_mv | AT tugbaertanbolelli discoveryofnewdnatopoisomeraseiiinhibitorsusingstructurebasedvirtualscreeningmethod AT kayhanbolelli discoveryofnewdnatopoisomeraseiiinhibitorsusingstructurebasedvirtualscreeningmethod |